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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Microglia modulate stable wakefulness via the thalamic reticular nucleus in mice
Hanxiao Liu1, Xinxing Wang1, Lu Chen1
1Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY, USA.
Abstract:
Microglia are important for brain homeostasis and immunity, but their role in regulating vigilance remains unclear. We employed genetic, physiological, and metabolomic methods to examine microglial involvement in the regulation of wakefulness and sleep. Microglial depletion decreased stable nighttime wakefulness in mice by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Metabolomic analysis revealed that the sleep-wake behavior closely correlated with diurnal variation of the brain ceramide, which disappeared in microglia-depleted mice. Ceramide preferentially influenced microglia in the thalamic reticular nucleus (TRN), and local depletion of TRN microglia produced similar impaired wakefulness. Chemogenetic manipulations of anterior TRN neurons showed that they regulated transitions between wakefulness and NREM sleep. Their firing capacity was suppressed by both microglial depletion and added ceramide. In microglia-depleted mice, activating anterior TRN neurons or inhibiting ceramide production both restored stable wakefulness. These findings demonstrate that microglia can modulate stable wakefulness through anterior TRN neurons via ceramide signaling.
Insights
Microglia regulate stable wakefulness through ceramide signaling in the brain. Microglial depletion impairs sleep-wake cycles by affecting thalamic neurons.
Area of Science:
- Neuroscience
- Immunology
- Sleep Science
Background:
- Microglia are key players in brain homeostasis and immunity.
- The specific role of microglia in regulating vigilance and sleep-wake cycles is not well understood.
Purpose of the Study:
- To investigate the involvement of microglia in the regulation of wakefulness and sleep.
- To elucidate the underlying molecular mechanisms, particularly the role of ceramide signaling.
Main Methods:
- Genetic microglial depletion in mice.
- Physiological monitoring of sleep-wake states.
- Brain metabolomic analysis.
- Chemogenetic manipulation of specific neuronal populations.
Main Results:
- Microglial depletion led to decreased stable nighttime wakefulness and increased wakefulness-NREM sleep transitions.
- Brain ceramide levels showed diurnal variation correlating with sleep-wake behavior, which was abolished upon microglial depletion.
- Ceramide influenced microglia in the thalamic reticular nucleus (TRN), and TRN microglial depletion impaired wakefulness.
- Anterior TRN neurons, modulated by microglia and ceramide, regulate wakefulness-NREM sleep transitions.
Conclusions:
- Microglia modulate stable wakefulness via ceramide signaling in the thalamic reticular nucleus.
- This pathway involves the regulation of anterior TRN neuron activity.
- Targeting microglial ceramide signaling may offer novel therapeutic strategies for sleep disorders.
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